A, The proportion of use of 99mTc-labeled radiotracer among cardiac stress tests with single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) shows a marked dip in mid-2010, corresponding to a period of severe disruptions in the worldwide 99mTc supply chain. During this period, there was a corresponding increase in the rate of cardiac catheterizations within 90 days after SPECT-MPI. B, Rates of SPECT-MPI, computed tomography coronary angiography, stress echocardiography, and positron emission tomography–MPI during this period are shown.
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Murthy VL, Lehrich J, Nallamothu BK. Cardiac Stress Testing and the Radiotracer Supply Chain: Nuclear Freeze. JAMA Cardiol. 2016;1(5):616–617. doi:10.1001/jamacardio.2016.1680
Nearly 15 million doses of technetium Tc 99m (99mTc) are used annually in the United States, most of which for cardiac stress testing with single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). Technetium Tc 99m is produced largely from “weapons-grade” highly enriched uranium (HEU). None of the nuclear reactors that produce molybdenum Mo 99 (99Mo), the parent isotope of 99mTc, are located in the United States and all are at least 50 years old, with repeated shortages of 99mTc occurring owing to required repairs. Although widely discussed,1,2 the clinical implications of these shortages have not been well studied. If 99mTc is unavailable, physicians may choose an older radiotracer, thallium Tl 201, or alternative tests. Such abrupt shifts could affect test quality and the use of downstream procedures including cardiac catheterization. We explored the clinical effects of a 6-month shortage (March-August 2010) for 99mTc resulting from shutdowns of 2 major nuclear reactors.
Using the 20% random sample of fee-for-service Medicare beneficiaries aged 65 years or older in the carrier and enrollment data from 2008 through 2012, we assessed 99mTc radiotracer use in the approximately 2 million cardiac stress tests with SPECT-MPI performed during these years, using codes A9500 and A9502 to identify 99mTc-labeled radiotracers. We calculated population-based rates of SPECT-MPI as well as rates for alternative testing modalities (stress echocardiography, computed tomography coronary angiography, and positron emission tomography–MPI) and downstream cardiac catheterization less than 90 days after index testing. We identified a priori the 6-month shortage during March through August 2010 due to shutdowns at the Petten High Flux and Chalk River Laboratories reactors, the 2 major producers of 99Mo for the United States. We used descriptive statistics to document temporal trends. Multivariable logistic regression was used to estimate the odds of cardiac catheterization less than 90 days after SPECT-MPI depending on radiotracer use after adjusting for age, sex, and race. This study was approved by the University of Michigan Institutional Review Board. Informed consent was waived for this retrospective study.
During the shortage, 99mTc use fell nearly one-fourth from 64% of SPECT-MPI in February 2010 just prior to the shortage to a low point of 49% in May 2010 (Figure, A). Despite a partial rebound after the shortage,99mTc use continued to decline, accounting for 52% of SPECT-MPI in September 2012. We observed steadily declining use of SPECT-MPI throughout the study period with stable rates of stress echocardiography, computed tomography coronary angiography, and positron emission tomography–MPI during the shortage (Figure, B). The adjusted odds of undergoing cardiac catheterization less than 90 days after SPECT-MPI was higher during the shortage (odds ratio = 1.09; 95% CI, 1.07-1.10; P < .001). Given the frequency of SPECT-MPI, 5715 excess cardiac catheterizations may have occurred among Medicare beneficiaries.
Recent shortages of 99mTc were associated with major shifts in its use during cardiac stress testing and an increase in downstream cardiac catheterization. Although changing referral patterns could contribute, we did not observe meaningful deviations from long-term trends in use of SPECT-MPI or alternative imaging tests during the shortage. This is supported by data from a Canadian hospital where downstream testing during the shortage of 99mTc increased by 77% and radiation exposures to patients doubled.3 Our study extends this finding to the United States nationally and raises a new concern of decreasing 99mTc use overall. Thallium Tl 201 is associated with higher radiation exposure4 and lower specificity relative to 99mTc.
Given tension between medical applications of HEU and potential for nuclear weapons proliferation, the US Congress authorized $143 million from 2011 to 2014 to encourage domestic production of 99mTc from sources other than HEU but has not renewed funding. Export of HEU fuel will be banned starting in 2020, which could severely curtail production of 99mTc. These converging pressures on the 99mTc supply chain have substantial clinical implications and underscore the importance of developing new production approaches and encouraging alternative testing approaches.
Corresponding Author: Venkatesh L. Murthy, MD, PhD, University of Michigan, 1338 Cardiovascular Center, 1500 E Medical Center Dr, SPC 5873, Ann Arbor, MI 48109 (firstname.lastname@example.org).
Published Online: June 29, 2016. doi:10.1001/jamacardio.2016.1680.
Author Contributions: Ms Lehrich had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Murthy, Nallamothu.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Murthy.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Murthy, Lehrich.
Obtained funding: Murthy.
Study supervision: Murthy, Nallamothu.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Murthy reported receiving a grant from the Intersocietal Accreditation Commission; holding stock in General Electric, Cardinal Health, and Mallinckrodt Pharmaceuticals; and receiving a grant and nonfinancial support from INVIA Medical Imaging Solutions. Dr Nallamothu reported receiving a grant from the Intersocietal Accreditation Commission; serving as associate editor for the American College of Cardiology (ACC.org) and the American Heart Association (Circulation: Cardiovascular Quality and Outcomes); and serving on an advisory board for UnitedHealthcare. No other disclosures were reported.